Polycystic ovary syndrome (PCOS) is the most common cause of female infertility in the United States. PCOS is classically characterized by hyperandrogenism and chronic anovulation, but it has become apparent that insulin resistance plays a central role in its pathogenesis. Insulin resistance increases long-term risks for development of type 2 diabetes, hypertension, dyslipidemia, hypercoaguability, and cardiovascular disease, the leading cause of death in American women. For decades, oral contraceptive pills (OCRs) have been standard therapy for women with PCOS not seeking pregnancy. OCPs create a hyperestrogenic state that favorably suppresses ovarian and androgen production. Although OCPs have several benefits in PCOS, limited evidence suggests that OCPs may worsen insulin resistance in PCOS. Therefore, the optimal pharmacotherapy for chronic management of PCOS remains unclear. The aim of this study is to determine whether the addition of an insulin-sensitizing agent to an OCP will ameliorate the adverse effects of hyperestrogenemia on the hyperinsulinemic insulin resistance of PCOS. Specifically, we will conduct a double-blind, randomized study that will determine if combination therapy of Metformin and ethinyl estradiol 35 mcg norgestimate, 0.25mg (Ortho-Cyclen, Ortho-McNeil Pharmaceuticals), compared to OCP monotherapy, will: 1) improve insulin sensitivity as measured directly by the frequently sampled intravenous glucose tolerance test (FSIVGTT); 2) favorably affect components of the metabolic syndrome; 3) reduce concentrations of inflammatory markers associated with cardiovascular risks (hsCRP, PAI-1, MCP-1, IL-6, VCAM-1, and ICAM-1); and 4) affect flow-mediated dilatation, a noninvasive measure of vascular endothelial cell nitric oxide availability. We hypothesize that combination therapy with an insulin-sensitizing drug and an OCP is the optimal maintenance therapy for PCOS to improve clinical, hormonal, and metabolic parameters and reduce long-term risks associated with insulin resistance. The results of this study will: 1) provide the groundwork for a larger randomized, controlled trial evaluating the effects of combination OCP-insulin sensitizer and other combination therapies on obese and lean women with PCOS; 2) provide data on the effects of hyperestrogenemia and insulin sensitization on diabetes and cardiovascular disease risk reduction, leading to a better understanding of mechanisms of insulin resistance in PCOS; and 3) lead to novel ways of managing chronic therapy of PCOS.